Re M C, Gibellini D, Furlini G, Vignoli M, Vitone F, Bon I, La Placa M
Department of Clinical and Experimental Medicine, Section of Microbiology, University of Bologna, Massarenti, Italy.
New Microbiol. 2001 Jul;24(3):207-15.
The possible relationships between the intensity of humoral response to full length Tat protein, the amount of proviral DNA reservoir in peripheral blood mononuclear cells and RNA viral load were analyzed in plasma samples obtained from a group of HIV-1 seropositive subjects, who never received any antiretroviral therapy. All HIV-1 patients showed detectable levels of serum IgG to full-length Tat by immunoenzymatic assay. We found a higher percentage of HIV-1 seropositive subjects with low levels of antibody in the presence of barely detectable proviral DNA copies (< or =10 copies/1.5x10(5) PBMCs) and a high anti-Tat antibody response accompanied by variable (from >10(1) to > or =10(3) copies/1.5x10(5) PBMCs) levels of DNA load (p=0.011). Moreover, an inverse relationship between anti-Tat antibody titers and HIV-1 RNA viral load was demonstrated HIV-1 seropositive patients. In HIV-1-infected patients, a strong humoral immune response against HIV-1 transactivating Tat protein, able to down-modulate viral replication in peripheral blood, does not seem to inhibit the number of proviral DNA molecules in peripheral blood mononuclear cells. Even though our data strongly confirm the "positive" role of anti-Tat antibody on viral replication, the persistence of significant amount of DNA viral load in peripheral blood mononuclear cells, despite high level of anti Tat antibody, suggests a more cautious approach to HIV-1 Tat-containing vaccines, able to stimulate an immune specific response to transactivating Tat protein sufficient in inhibiting circulating virus, but not completely efficient in decreasing proviral DNA integration.
在一组从未接受过任何抗逆转录病毒治疗的HIV-1血清阳性受试者的血浆样本中,分析了针对全长Tat蛋白的体液反应强度、外周血单核细胞中前病毒DNA储存库的数量与RNA病毒载量之间的可能关系。通过免疫酶测定法,所有HIV-1患者的血清IgG对全长Tat均呈现可检测水平。我们发现,在前病毒DNA拷贝数几乎检测不到(≤10拷贝/1.5x10⁵外周血单核细胞)的情况下,HIV-1血清阳性受试者中抗体水平低的比例更高,而高抗Tat抗体反应伴随着不同水平(从>10¹到≥10³拷贝/1.5x10⁵外周血单核细胞)的DNA载量(p = 0.011)。此外,在HIV-1血清阳性患者中,抗Tat抗体滴度与HIV-1 RNA病毒载量之间呈负相关。在HIV-1感染患者中,针对HIV-1反式激活Tat蛋白的强大体液免疫反应虽能下调外周血中的病毒复制,但似乎并未抑制外周血单核细胞中前病毒DNA分子的数量。尽管我们的数据有力地证实了抗Tat抗体对病毒复制的“积极”作用,但尽管抗Tat抗体水平很高,外周血单核细胞中仍存在大量DNA病毒载量,这表明对于含HIV-1 Tat的疫苗应采取更为谨慎的方法,这种疫苗能够刺激对反式激活Tat蛋白的特异性免疫反应,足以抑制循环病毒,但在减少前病毒DNA整合方面并非完全有效。